At a bustling recording studio in New York City, Eddie Kearns performs "The Broadway Melody," excitedly sharing with some chorus girls that he has brought the Mahoney Sisters' vaudeville act to the city for a special performance in a new revue directed by the renowned producer Francis Zanfield. The sisters, Harriet "Hank" Mahoney (Bessie Love) and Queenie Mahoney (Anita Page), eagerly await Eddie's arrival at their hotel apartment located on 46th Street. Hank, the elder sister, prides herself on her business acumen and artistic talent, while Queenie is celebrated for her stunning beauty. Although Hank is confident about their future success, Queenie harbors doubts about staking everything for fame.
Their Uncle Jed, a brief visitor, proposes a 30-week traveling show, which Hank declines, though she agrees to reflect on it. As Eddie arrives, he is taken aback by Queenie's beauty, having not seen her since she was a child. He prompts them to join him for a rehearsal with Zanfield. During their audition at the theater, a mysterious blonde woman sabotages their performance by placing a bag inside the piano, leading to a physical altercation with Hank. Although Zanfield shows little interest in their act, he expresses curiosity about Queenie, to whom she pleads to secure a role for Hank as well, insisting that they can work great together for one salary.
A dress rehearsal soon reveals trouble, as Zanfield claims that the pacing of "The Broadway Melody" requires cuts to Hank and Queenie's parts. Meanwhile, an accident involving a set prop results in Queenie being chosen as a replacement, quickly captivating the audience and the wealthy playboy, Jacques "Jock" Warriner. Although Jock's attention delights Queenie, it provokes Hank's disapproval, as she feels that her sister is prioritizing her looks over her talent.
Over the next couple of weeks, Queenie and Jock grow closer, igniting tension with both Hank and Eddie, who adamantly oppose the relationship. This strain leads Queenie to distance herself from them, worsened by her feelings for Eddie that she struggles to confront. Eventually, Eddie and Queenie confess their love, but Queenie pushes Eddie away to preserve her sister's feelings. Following an emotional confrontation where Hank realizes their true love for one another, she harshly tells Eddie to pursue Queenie, claiming she never truly loved him and utilizing him solely for personal gain.
After Eddie's departure, Hank experiences a whirlwind of emotions, oscillating between tears and laughter, before ultimately accepting the traveling show proposal. Later, a wild party takes place at Jock's new apartment for Queenie. As Jock attempts to force his advances, a heroic Eddie confronts him, leading to a physical altercation where Eddie is overpowered. True to herself, Queenie rushes to Eddie and abandons Jock, leaving chaos behind.
In a final twist of fate, Hank and Uncle Jed eagerly await the return of Queenie and Eddie from their honeymoon, indicating a possible reconciliation between the sisters. However, beneath their joyful reunion lies an underlying tension between Hank and Eddie. Queenie decides to leave show business and make a home on Long Island, insisting that Hank must live with them after her obligations conclude. After Hank departs with her new partner, Queenie finds herself lamenting that she could not assist her sister in securing her happiness. In a shocking turn, Hank's new partner is the same blonde woman who sabotaged their earlier performance. The film concludes with Hank, Uncle Jed, and her new partner taking a taxi to the train station, with Hank vowing they will make a triumphant return to Broadway in just six months.
